Flatfish constitute a natural paradigm to investigate adaptive changes in the central nervous system of vertebrates. During their metamorphosis, vestibular and oculomotor coordinates rotate 90 degree relative to each other. Although the adult fish has a bilaterally asymmetric appearance, there is a central reconstitution of symmetry in the vestibulo-oculomotor system. Thus, the maintenance of symmetry appears to be an important operational principle of brain function. The proposed research will focus on the question of central nervous symmetry within the vestibulo-oculomotor system of the morphologically asymmetric flatfish and on the factors triggering re-establishment of symmetry during metamorphosis of the fish. In regard to the SYMMETRIC ORGANIZATION of the vestibulo- ocular reflex system at the three-neuron-arc level in the adult flatfish, the central representation of otolithic, optokinetic and eye-movement related signals and the underlying circuitry will be determined. Neuroethological, electrophysiological and neuroanatomical (extra- and intracellular HRP, WGA-HRP) method will be used. In premetamorphic and metamorphosing flatfish, the ontogenetic development of the adaptive reflex in regard to behavior, vestibular nucleus activity, and the development of specific inhibitory neurotransmitters within vertical and horizontal systems (GABA, glycine) will be investigated. The methods to be utilized encompass eye movement analysis via video-recordings, (14C)-2-deoxyglucose autoradiography, and also immunohistochemistry and electronmicroscopy. In addition, the more general question of INDUCTION OF METAMORPHOSIS will be addressed at the systemic endocrinological level by application of thyroxin antagonists, and at the species-specific level of the flatfish by utilizing chemical (streptomycin, kainic acid) and surgical lesion experiments in the vestibular and olivo-cerebellar systems, as well as natural sensory deprivation to the visual system. The proposed experiments will describe comprehensively the entire three-neuron-arc-vestibulo-ocular reflex system and its symmetric central representation in the asymmetric adult flatfish. The long-term plans of this research target the spatial and temporal mechanisms involved in the transition from premetamorphic to postmetamorphic symmetry and questions about induction of metamorphosis in the flatfish in particular, and vertebrates, in general.